Inflammation-triggered andrographolide nanoprodrug platform for lung-targeted delivery and immune homeostasis recovery: A therapeutic strategy against cytokine storm
Abstract
Acute lung injury (ALI) leads to severe pulmonary inflammation and alveolar-capillary barrier disruption, with therapy limited by poor solubility and bioavailability of anti-inflammatory agents. To address the limited aqueous solubility, insufficient lesion accumulation, and poor bioavailability of andrographolide (ANDRO) in ALI therapy, an inflammation-responsive nanoprodrug platform (NanoPro5000@ANDRO) was developed via subcomponent self-assembly using dynamic boronic ester and imine linkages, thereby enabling both chemical conjugation and physical encapsulation of ANDRO at a total drug-loading content of 30.24% with an average hydrodynamic diameter of 206.4 nm. This platform exhibited excellent biocompatibility, including a hemolysis rate of <5% and protein adsorption of <10%, and achieved 82.1% cumulative ANDRO release at 48 h under acidic and oxidative conditions, facilitating inflammation-associated lesion-specific drug delivery. Furthermore, the nanosystem exhibited enhanced pulmonary accumulation in inflamed lung tissues, suppressed pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin (IL)-6, upregulated anti-inflammatory mediators, including IL-4 and IL-10, reduced oxidative stress, and promoted M2 macrophage polarization. These combined effects alleviated cytokine storm, restored inflammatory microenvironment homeostasis, and attenuated lipopolysaccharide-induced ALI-associated tissue damage with confirmed biosafety. Overall, this study presents a dual dynamic covalent bond-based nanoprodrug strategy featuring dual ANDRO loading and pH/reactive oxygen species-responsive release behavior, providing a promising therapeutic approach for cytokine-associated inflammatory pulmonary diseases.
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BibTeX
@article{zhou2026inflammationtriggered,
title = {{Inflammation-triggered andrographolide nanoprodrug platform for lung-targeted delivery and immune homeostasis recovery: A therapeutic strategy against cytokine storm}},
author = {Yin Zhou and Jiayi Wang and Yi Chen and Zijie Li and Gustavo Puras and José Luis Pedraz and Zhongwei Gu and Yiyan He},
journal = {Asian Journal of Pharmaceutical Sciences},
year = {2026},
month = sep,
doi = {10.1016/j.ajps.2026.101200},
url = {https://doi.org/10.1016/j.ajps.2026.101200},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Inflammation-triggered andrographolide nanoprodrug platform for lung-targeted delivery and immune homeostasis recovery: A therapeutic strategy against cytokine storm
AU - Yin Zhou
AU - Jiayi Wang
AU - Yi Chen
AU - Zijie Li
AU - Gustavo Puras
AU - José Luis Pedraz
AU - Zhongwei Gu
AU - Yiyan He
PY - 2026
DA - 2026/09/12
JO - Asian Journal of Pharmaceutical Sciences
DO - 10.1016/j.ajps.2026.101200
UR - https://doi.org/10.1016/j.ajps.2026.101200
AB - Acute lung injury (ALI) leads to severe pulmonary inflammation and alveolar-capillary barrier disruption, with therapy limited by poor solubility and bioavailability of anti-inflammatory agents. To address the limited aqueous solubility, insufficient lesion accumulation, and poor bioavailability of andrographolide (ANDRO) in ALI therapy, an inflammation-responsive nanoprodrug platform (NanoPro5000@ANDRO) was developed via subcomponent self-assembly using dynamic boronic ester and imine linkages, thereby enabling both chemical conjugation and physical encapsulation of ANDRO at a total drug-loading content of 30.24% with an average hydrodynamic diameter of 206.4 nm. This platform exhibited excellent biocompatibility, including a hemolysis rate of <5% and protein adsorption of <10%, and achieved 82.1% cumulative ANDRO release at 48 h under acidic and oxidative conditions, facilitating inflammation-associated lesion-specific drug delivery. Furthermore, the nanosystem exhibited enhanced pulmonary accumulation in inflamed lung tissues, suppressed pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin (IL)-6, upregulated anti-inflammatory mediators, including IL-4 and IL-10, reduced oxidative stress, and promoted M2 macrophage polarization. These combined effects alleviated cytokine storm, restored inflammatory microenvironment homeostasis, and attenuated lipopolysaccharide-induced ALI-associated tissue damage with confirmed biosafety. Overall, this study presents a dual dynamic covalent bond-based nanoprodrug strategy featuring dual ANDRO loading and pH/reactive oxygen species-responsive release behavior, providing a promising therapeutic approach for cytokine-associated inflammatory pulmonary diseases.
SN - 1818-0876
SN - 2221-285X
ER -